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Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

Drug Interactions

Drug Interactions between Nucleoside Reverse Transcriptase Inhibitors and Other Drugs (Including Antiretroviral Agents)

(Last updated: April 8, 2015; last reviewed: April 8, 2015)

Table 19c. Drug Interactions Between Nucleoside Reverse Transcriptase Inhibitors and Other Drugs (Including Antiretroviral Agents)
Concomitant Drug
NRTI Effect on NRTI and/or Concomitant Drug Concentrations Dosage Recommendations and Clinical Comments
Non-ARV Antivirals
Adefovir TDF No data Do not coadminister. Serum concentrations of TDF and/or other renally eliminated drugs may be increased.
TDF No data Serum concentrations of these drugs and/or TDF may be increased. Monitor for dose-related toxicities.
ZDV No significant effect Potential increase in hematologic toxicities
  • Ledipasvir ↑ TDF AUC 40% to 98% when TDF given with RPV and EFV
  • Further ↑ TDF possible if TDF given with PIs
No dose adjustment necessary. Monitor for TDF toxicity.

The safety of increased TDF exposure when ledipasvir/sofosbuvir is coadministered with TDF and a PI/r, ATV/c, or DRV/c has not been established. Consider alternative HCV or ARV drugs to avoid increased TDF toxicities. If coadministration is necessary, monitor for TDF-associated adverse reactions.

Coadministration of ledipasvir/sofosbuvir with EVG/c/TDF/FTC is not recommended.
Ribavirin ddI ↑ intracellular ddI Contraindicated. Do not coadminister. Fatal hepatic failure and other ddI-related toxicities have been reported with coadministration.
ZDV Ribavirin inhibits phosphorylation of ZDV. Avoid coadministration if possible, or closely monitor HIV virologic response and possible hematologic toxicities.
  • TDF AUC ↑ 12% and Cmin ↑ 19%
  • DTG ↔
No dosage adjustment necessary.
RAL TDF RAL AUC ↑ 49% No dosage adjustment necessary.
Narcotics/Treatment for Opioid Dependence
Buprenorphine 3TC, ddI, TDF, ZDV No significant effect No dosage adjustment necessary.
Methadone ABC methadone clearance ↑ 22% No dosage adjustment necessary.
d4T d4T AUC ↓ 23% No dosage adjustment necessary.
ZDV ZDV AUC ↑ 29% to 43% Monitor for ZDV-related adverse effects.
ddI d4T No significant PK interaction Do not coadminister. Additive toxicities of peripheral neuropathy, lactic acidosis, and pancreatitis seen with this combination.
TDF ddI-EC AUC and Cmax ↑ 48% to 60% Avoid co-administration.
Allopurinol ddI ddI AUC ↑ 113%
In patients with renal impairment:
  • ddI AUC ↑ 312%
Contraindicated. Potential for increased ddI-associated toxicities.
Monitor for ZDV-related adverse effects.
ddI With ddI-EC plus ATV (with food):
  • ddI AUC ↓ 34%
  • ATV no change
Administer ATV with food 2 hours before or 1 hour after ddI.
TDF With ATV (unboosted):
  • ATV AUC ↓ 25% and Cmin ↓ 23% to 40% (higher Cmin with RTV than without RTV)
  • TDF AUC ↑ 24% to 37%
Avoid concomitant use without RTV or COBI. Dose:
  • ATV 300 mg daily plus (RTV 100 mg or COBI 150 mg) daily when coadministered with TDF 300 mg daily. 
  • If using TDF and H2 receptor antagonist in ART-experienced patients, use ATV 400 mg daily plus (RTV 100 mg or COBI 150 mg) daily.
Monitor for TDF-associated toxicity. 
ZDV With ATV (unboosted):
  • ZDV Cmin ↓ 30% and AUC ↔
Clinical significance unknown.
DVR/c TDF Increased TDF possible Monitor for TDF-associated toxicity.
DRV/r TDF TDF AUC ↑ 22% and Cmin ↑ 37%
Clinical significance unknown. Monitor for TDF toxicity.
  • LPV/r AUC ↓ 15%
  • TDF AUC ↑ 34%
Clinical significance unknown. Monitor for TDF toxicity.
TPV/r ABC ABC AUC ↓ 35% to 44%
Appropriate doses for this combination have not been established.
  • ddI-EC AUC ↔ and Cmin ↓ 34%
  • TPV/r ↔
Separate doses by at least 2 hours.
  • TDF AUC ↔
  • TPV/r AUC ↓ 9% to 18% and Cmin ↓ 12% to 21%
No dosage adjustment necessary.
  • ZDV AUC ↓ 35%
  • TPV/r AUC ↓ 31% to 43% 
Appropriate doses for this combination have not been established.
Key to Symbols: ↑ = increase, ↓ = decrease, ↔ = no change

Key to Abbreviations: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; ATC/c = atazanavir/cobicistat; AUC = area under the curve; Cmax  = maximum plasma concentration; Cmin = minimum plasma concentration; COBI = cobicistat; d4T = stavudine; ddI = didanosine; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = douletegravir; EC = enteric coated; EFV = efavirenz; EVG/c/TDF/FTC = elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine; HCV = hepatitis C virus; INSTI = integrase strand transfer inhibitor; LPV/r = lopinavir/ritonavir; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PI/r = ritonavir-boosted protease inhibitor; PK = pharmacokinetic; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; TDF = tenofovir disoproxil fumarate; TPV/r = tipranavir/ritonavir; ZDV = zidovudine

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